Please use this identifier to cite or link to this item: http://hdl.handle.net/1822/25145

TitleRKIP Inhibition in cervical cancer Is associated with higher tumor aggressive behavior and resistance to cisplatin therapy
Author(s)Martinho, Olga
Pinto, Filipe
Granja, Sara Costa
Gonçalves, Vera M.
Longatto Filho, Adhemar
Reis, R. M.
Loreto, Celso di
Rosner, Marsha R.
Moreira, Marise A. R.
Ribeiro, Luís F. J.
Issue date2013
PublisherPublic Library of Science (PLOS)
JournalPLoS ONE
Abstract(s)Cervical cancer is one of the most common cancers in women worldwide, being high-risk group the HPV infected, the leading etiological factor. The raf kinase inhibitory protein (RKIP) has been associated with tumor progression and metastasis in several human neoplasms, however its role on cervical cancer is unclear. In the present study, 259 uterine cervix tissues, including cervicitis, cervical intraepithelial lesions and carcinomas, were analyzed for RKIP expression by immunohistochemistry. We found that RKIP expression was significantly decreased during malignant progression, being highly expressed in non-neoplastic tissues (54% of the samples; 73/135), and expressed at low levels in the cervix invasive carcinomas (,15% (19/124). Following in vitro downregulation of RKIP, we observed a viability and proliferative advantage of RKIP-inhibited cells over time, which was associated with an altered cell cycle distribution and higher colony number in a colony formation assay. An in vitro wound healing assay showed that RKIP abrogation is associated with increased migratory capability. RKIP downregulation was also associated with an increased vascularization of the tumors in vivo using a CAM assay. Furthermore, RKIP inhibition induced cervical cancer cells apoptotic resistance to cisplatin treatment. In conclusion, we described that RKIP protein is significantly depleted during the malignant progression of cervical tumors. Despite the lack of association with patient clinical outcome, we demonstrate, in vitro and in vivo, that loss of RKIP expression can be one of the factors that are behind the aggressiveness, malignant progression and chemotherapy resistance of cervical cancer.
TypeArticle
URIhttp://hdl.handle.net/1822/25145
DOI10.1371/journal.pone.0059104
ISSN1932-6203
Publisher versionhttp://www.plosone.org
Peer-Reviewedyes
AccessOpen access
Appears in Collections:ICVS - Artigos em Revistas Internacionais com Referee

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